An immunogenomic exome landscape of triple positive primary antiphospholipid patients.

Primary antiphospholipid syndrome is characterized by thrombosis and autoantibodies directed against phospholipids or associated proteins. The genetic etiology of PAPS remains unknown. We enrolled 21 patients with thromboembolic events associated to lupus anticoagulant, anticardiolipin and anti ß2 glycoprotein1 autoantibodies. We performed whole exome sequencing and a systematic variant-based analysis in genes associated with thrombosis, in candidate genes previously associated with APS or inborn errors of immunity. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. Variants were identified following a state-of-the-art pipeline. Enrichment analysis was performed by comparing with the control cohort. We found an absence of significant HLA bias and genetic heterogeneity in these patients, including when testing combinations of rare variants in genes encoding for proteins involved in thrombosis and of variants in genes linked with inborn errors of immunity. These results provide evidence of genetic heterogeneity in PAPS, even in a homogenous series of triple positive patients. At the individual scale, a combination of variants may participate to the breakdown of B cell tolerance and to the vessel damage.

Infant arousal in an en-face exchange with a new partner: effects of prematurity and perinatal biological risk.

Very low birth weight (VLBW) infants of higher (n = 18) and lower (n = 29) perinatal biological risk were contrasted at 4 months adjusted age with healthy full-term infants (n = 32) in their arousal during a standardized peekaboo game with an examiner. VLBW infants showed less positive arousal, more negative arousal, and 3 mixtures of behavioral cues across the peekaboo game seldom seen for full-term infants-strong cues of both positive and negative arousal, strong cues of negative arousal alone, and no strong cues of either positive or negative arousal. Contrary to expectations, perinatal biological risk did not strongly predict variations in arousal within the VLBW group. Possible changes in how internal and external sources of arousal are integrated provide one explanation for the presence of strong relationships between perinatal biological risk and social responsiveness near term age and their disappearance by 4 months of age.

Reproducibility of irregular radiation fields for malignant lymphoma.

PURPOSE: Radiation treatment for malignant lymphoma requires large field irradiation with irregular blocks according to the individual anatomy and tumor configuration. For determination of safety margins (PTV) we quantitatively analysed the accuracy of field and block placement with regard to different anatomical regions. PATIENTS AND METHODS: Forty patients with malignant lymphoma were irradiated using the classical supra-/infradiaphragmatic field arrangements. Treatment was performed with 10-MeV photons and irregularly shaped, large opposing fields. We evaluated the accuracy of field and block placements during the treatment courses by comparing the regularly performed verification-with the simulation films. Deviations were determined with respect to the field edges and the central axis, along the x- and z-axis. RESULTS: With regard to the field edges, mean deviations of 2.0 mm and 3.4 mm were found along the x- and z-axis. The corresponding standard deviations were 3.4 mm and 5.5 mm, respectively. With regard to the shielding blocks, mean displacement along the x- and z-axis was 2.2 mm and 3.8 mm. In addition, overall standard deviations of 5.7 mm (x-axis) and 7.1 mm (z-axis) were determined. During the course of time an improved accuracy of block placement was notable. CONCLUSION: Systematic analysis of port films gives information for a better defining safety margins in external radiotherapy. Evaluation of verification films on a regular basis improves set-up accuracy by reducing displacements.